The Project was linked to a broader multicenter international case-control study on selected environmental risk factors for MS, that Dr. Maura Pugliatti (Project PI and post-doc at UiB) is co-coordinating in collaboration with UiB, MS National Competence Centre, Haukeland University Hospital, McGill University, Montreal, Canada.

REPORT OF ACTIVITIES (YEAR 2009)

The Project was linked and nested within a broader research focus regarding the design of a multicenter international case-control study on selected environmental risk factors for MS, that Dr. Maura Pugliatti (Project PI and post-doc at UiB) is co-coordinating with Prof. Trond Riise (Dept. of Public Health and Primary Health Care, UiB), Prof. Kjell-Morten Myhr (MS National Competence Centre, Haukeland University Hospital, Bergen) and Prof. Christina Wolfson (McGill University, Montreal, Canada).

All project specific activities were performed during year 2008. All throughout year 2009 the project results contributed to assessing exposure to vitamin D by means of population-specific questionnaires within the international case-control study.

In particular, the international case-control study, the largest ever conducted in MS, was launched in May 2009 and included ca. 5000 MS-patients and 20000 healthy subjects. It has received further financial support in year 2008 from the Italian MS Foundation (Fondazione Italiana Sclerosi Multipla). The same number of questionnaires were sent to the participants via post mail and by means of two mailings. The Norwegian substudy is over with a response rate of ca. 50%, whereas the Sardinian substudy is taking place now.

Questions on vitamin D intake through diet, use of supplements and sunlight exposure during childhood and adolescence have been designed for the Norwegian and for the Italian population with the consultancy of a nutritionist, Dr. Maria Parpinel, University of Udine, Italy. The sections aimed at assessing past vitamin D status have similar if not identical design for both study sites, have been edited in English first, and subsequently translated into Norwegian and Italian. As for diet, particular focus was given on the past consumption of fish (amount and frequency), calcium intake (milk and dairy products, water), and vitamin supplements. To assess past sun exposure we selected questions that had already been shown to have good test-retest reliability and have been validated by others [van der Mei et al, 2003; van der Mei et al, 2006; Kampman et al, 2007].

Based on the preliminary results obtained with the financial contribution of the present Project, the study has in fact received further funding from Helse Vest, Norway for a 1-year project (Principal Investigator: Prof. Kjell-Morten Myhr, grant n. 911474/2009) and from the Italian MS Foundation (FISM) for a 2-year project (Principal Investigator: Dr. Maura Pugliatti, extension of grant n. 19/R/2008).

Data collection will take place in 2010 by means of scanning and optical reading at the Dept. of Public Health and Primary Health Care, University of Bergen.

The analysis plan will be standard for case-control studies using unconditional logistic regression to examine the main effects for the overall study. For the overall study, country will be considered first as an effect modifier and in the absence of evidence of effect modification, country will be considered as a potential confounder.

An important goal of the study will be achieved by examining possible interactions between the independent variables, again by using logistic regression models.

2008

Role of vitD in shaping population-specific occurrence of MS

The Project focused on outlining a common methodology and designing a postal questionnaire to assess the past vitamin D status through diet, supplements and sunlight exposure in Norway and Sardinia, Italy. Two pilot studies ensured cross-culturally acceptability, user friendliness, and feasibility to complete for MS patients and healthy subjects.

The international case-control study, the largest ever conducted in MS, will be launched in 2009 and will include over 4000 MS-patients and 16000 healthy subjects. Data on past exposures are collected using a standardized self administered postal questionnaire.

The proposal was focused on outlining the methodology and designing instruments to assess and compare the vitamin D status through past exposure between two different epidemiological settings (Norway and Sardinia, insular Italy) and same methodological approach.

Comparable questions on vitamin D intake through diet, use of supplements and sunlight exposure during childhood and adolescence have been designed for the Norwegian and Italian/Sardinian population with nutritionists’ consultancy. They were edited in English first, and translated into Norwegian and Italian. Particular focus was given on the past consumption of fish (amount and frequency), milk and dairy products, water, and vitamin supplements. To assess past sun exposure questions that had already been shown to have good test-retest reliability and had been validated by others [van der Mei et al, 2003; van der Mei et al, 2006; Kampman et al, 2007] were selected.

Two pilot studies to ensure a user friendly, easy to understand and easy to complete questionnaire were conducted. In March 2008 we pre-tested the questionnaire on Sardinian and Norwegian MS patients and healthy subjects. Scores of 1 were reported by over 53% for recalled diet and over 70% for sun exposure. Neither sex nor subject group was found to be related to the level of understanding/difficulty. The questionnaire proved to be cross-culturally acceptable and feasible to complete to the same degree in MS patients and healthy subjects, and an appropriate tool for assessing the association between MS risk and past environmental exposure in large international case-control studies. The results were presented at the meeting of the 2008 World Committee for Treatment and Research in MS (WCTRIMS).

Based on these results, the questionnaire was modified, professionally printed (Bording AS) and a second pilot test was performed in November 2008. The questions were found generally easy to understand and to answer (score 1). For all modified items the mean scores were lower compared to the previous pilot study. Internal validation of selected items using the pilot data was done. The skin colour measured by ticking off on a printed colour scale showed a good correlation with responses to questions on tanning reaction to sun exposure within the participating areas. The correlation between current body shape and reported actual weight was highly consistent. The results will be submitted to the 2009 American Committee for Treatment and Research in MS (ACTRIMS).

A test-retest reliability assessment of the latest revised version is ongoing (January 2009).

With the financial contribution of Helse Vest, two workshops took place in 2008, aimed at finalizing the questionnaire: one in Alghero, Italy (April 4-5), and one in Venice, Italy (December 12-13).